scholarly journals Differences in the On- and Off-Tumor Microbiota between Right- and Left-Sided Colorectal Cancer

2021 ◽  
Vol 9 (5) ◽  
pp. 1108
Author(s):  
Oliver Phipps ◽  
Mohammed N. Quraishi ◽  
Edward A. Dickson ◽  
Helen Steed ◽  
Aditi Kumar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Rna ◽  
Colorectal Adenocarcinoma ◽  
Left Colon ◽  
Bacterial Taxonomy ◽  
Bacterial Populations ◽  
Alpha And Beta Diversity ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Microbiome Profiling

This study aims to determine differences in the on- and off-tumor microbiota between patients with right- and left-sided colorectal cancer. Microbiome profiling of tumor and tumor-adjacent biopsies from patients with right-sided (n = 17) and left-sided (n = 7) colorectal adenocarcinoma was performed using 16S ribosomal RNA sequencing. Off-tumor alpha and beta diversity were significantly different between right- and left-sided colorectal cancer patients. However, no differences in on-tumor diversity were observed between tumor locations. Comparing the off-tumor microbiota showed the right colon to be enriched with species of the Lachnoclostridium, Selenomonas, and Ruminococcus genera. Whereas the left colon is enriched with Epsilonbacteraeota phylum, Campylobacteria class, and Pasteurellales and Campylobacterales orders, in contrast, the on-tumor microbiota showed relatively fewer differences in bacterial taxonomy between tumor sites, with left tumors being enriched with Methylophilaceae and Vadin BE97 families and Alloprevotella, Intestinibacter, Romboutsia, and Ruminococcus 2 genera. Patients with left-sided colorectal cancer had large taxonomic differences between their paired on- and off-tumor microbiota, while patients with right-sided colorectal cancer showed relatively fewer taxonomic differences. Collectively, this suggests that the right and left colon show distinctive bacterial populations; however, the presence of a colonic tumor leads to a more consistent microbiota between locations.

scholarly journals Differences in the on- and off-tumour microbiota between right- and left-sided colorectal cancer

2021 ◽  
Author(s):  
Oliver Phipps ◽  
Mohammed N Quraishi ◽  
Edward A Dickson ◽  
Jonathan Segal ◽  
Helen Steed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Beta Diversity ◽  
Alpha Diversity ◽  
Left Colon ◽  
Bacterial Taxonomy ◽  
Microbial Profiling ◽  
Registration Number ◽  
Colonic Tumour ◽  
The Right ◽  
Colorectal Cancer Patients

Abstract Objective This study aims to determine the differences in the microbial profiles of the on- and off-tumour microbiota between patients with right- and left-sided colorectal cancer.Design Microbial profiling of on- and off-tumour biopsies from patients with right-sided (n=17) and left-sided (n=7) colorectal adenocarcinoma was performed using 16S ribosomal RNA sequencing. Results Off-tumour alpha diversity is significantly greater in right-sided compared to left-sided colorectal cancer patients. However, no differences in on-tumour alpha diversity were observed between tumour locations. Off-tumour beta diversity showed distinctive bacterial community clusters between the right and left colon, while no significant differences in beta diversity were observed in the on-tumour microbiota. The off-tumour microbiota showed the right colon to be enriched with species of the Lachnoclostridium, Selenomonas and Ruminococcus genera, whereas the left colon is enriched with Epsilonbacteraeota phylum, Campylobacteria class, and Pasteurellales and Campylobacterales orders. In contrast the on-tumour microbiota showed relatively fewer differences in bacterial taxonomy between tumour sites, with left tumours being enriched with Methylophilaceae and Vadin BE97 families and Alloprevotella, Intestinibacter, Romboutsia and Ruminococcus 2 genera. Comparison of paired on- and off-tumour microbiotas showed that patients with left-sided colorectal cancer had large taxonomic differences between their on- and off-tumour microbiota, while patients with right-sided colorectal cancer showed relatively fewer taxonomic differences.Conclusion The off-tumour microbiota is more diverse in the right compared to the left colon, showing distinct community clusters and large differences in bacterial taxonomy. In contrast the on-tumour microbiota shows no difference in bacterial diversity and relatively fewer differences in bacterial taxonomy. Collectively this suggests that the right and left colon show distinctive bacterial communities, however, the presence of a colonic tumour leads to a more consistent microbiota between locations. Trial registration number clinicaltrials.gov (NCT01701310).

scholarly journals LRIG1 Expression and Colorectal Cancer Prognosis

2020 ◽  
Author(s):  
Maryam Bakherad ◽  
Mahdieh Salimi ◽  
Seyed Abdolhamid Angaji ◽  
Frouzandeh Mahjoubi ◽  
Tayebeh Majidizadeh
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Cancer Prognosis ◽  
Protein Levels ◽  
Tumor Tissues ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Leucine Rich Repeats ◽  
And Control

Abstract BackgroundTo make the right treatment decisions about colorectal cancer (CRC) patients reliable predictive and prognostic data are needed. However, in many cases this data is not enough. Some studies suggest that LRIG1 gene (leucine-rich repeats and immunoglobulin-like domains1) has prognostic implications in different kinds of cancers. MethodsOne hundred and two patients with colorectal cancer were retrospectively analyzed for LRIG1 expression at both mRNA and protein levels. SYBR Green Real-Time RT-PCR technique was used for mRNA expression analyses and Glyceraldehyde-3-Phosphate Dehydrogenase gene (GAPDH) was considered as a reference gene for data normalization. LRIG1 protein expression was analyzed using Immunohistochemistry (IHC). Additionally, appropriate statistic analyses were used to assess the expression of LRIG1 in test and control groups. The prognostic significance of LRIG1 expression was analyzed using the univariate and multivariate analyses.ResultsThe data revealed that the expression of LRIG1 in both mRNA and protein levels was down regulated in colorectal tumor tissues (P<0.01) but is not clinically relevant prognostic indicator in CRC. ConclusionsTherefore, it is suggested that LRIG1 expression analyses may not be considered as an important issue when making informed and individualized clinical decisions regarding the management of colorectal cancer patients.

Assay result variability during determination of mismatch repair deficiency status using immunohistochemistry: A transatlantic comparative study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 403-403
Author(s):  
G. Hutchins ◽  
K. Handley ◽  
F. L. Baehner ◽  
M. Lopatin ◽  
H. Yaziji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Tissue Microarrays ◽  
Cancer Trial ◽  
Colon Cancers ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Material ◽  
The Right ◽  
Colorectal Cancer Patients

403 Background: Colorectal cancer patients with deficient mismatch repair (dMMR) have significantly fewer recurrences and may respond less well to chemotherapy. Immunohistochemical (IHC) determination of MMR status is therefore recommended to identify patients in whom adjuvant therapy is not indicated, but little is known regarding the variability of assay results. We aimed to define MMR IHC assay variability in formalin-fixed, paraffin-embedded (FFPE) material from the QUASAR-1 colorectal cancer trial contained within heterogeneity-prone tissue microarrays (TMAs) Methods: TMA sections of FFPE material from the QUASAR-1 trial were distributed to 2 independent laboratories (Leeds, UK and Vitro Molecular Laboratories [VML], FL, USA) for MMR IHC assays. Serial TMA sections were stained with MLH1/MSH2 using techniques blinded to the other laboratory. Each stained section was double-scored independently and results compared to determine inter-assay variability. Results: Matched MMR data were available for 1224 cases of MLH1 and 1223 cases of MSH2. Of these, loss of expression of MMR (dMMR) was reported in 160 cases (13.1%) by VML and 179 cases (14.6%) by Leeds. 140 (11.4%) were dMMR in both labs, 20 cases (1.6%) by VML alone and 39 (3.2%) by Leeds alone. Discordant dMMR status was observed in 56/166 (34%) dMMR cases identified with MLH1 and 10/34 (29%) cases identified with MSH2. Kappa coefficients for inter-assay agreement were 0.798 (95% CI = 0.748 - 0.848) for MMR status overall, 0.778 (95% CI = 0.722 - 0.835) for MLH1 and 0.823 (95% CI = 0.714 - 0.932) for MSH2. 85% (33/39) of discordant Leeds dMMR colon cancers were in the right colon where dMMR is more common, compared to 47% of VML discordant dMMR cases. Conclusions: Independent determination of MMR status by IHC on TMAs is associated with excellent inter-assay agreement. The reasons for MMR case discordance are under further investigation. These results further support routine MMR testing by IHC. No significant financial relationships to disclose.

Oncogenic mutations in colorectal cancer, indications for anatomical sites, and targeted intervention.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22037-e22037
Author(s):  
Giovanni Corso ◽  
Valeria Pascale ◽  
Giuseppe Flauti ◽  
Daniele Marrelli ◽  
Franco Roviello
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Left Colon ◽  
Targeted Intervention ◽  
Right Colon ◽  
Right Colon Cancer ◽  
Oncogenic Mutations ◽  
Colorectal Cancer Patients

e22037 Background: Oncogenic mutations, such as KRAS, in colorectal cancer patients are considered standard molecular biomarkers that predict the clinical benefit for the targeted intervention with EGFR inhibitors. In addition, these mutations are associated with specific anatomical area in the colon tumor development, as BRAF mutations with the microsatellite instability. Methods: In this translational study we aim to assess the mutation frequencies of the EGFR [hotspot area and polyadenine deletions (A13_del)], KRAS, BRAFV600E, and PIK3CA oncogenes in a series of 280 colorectal cancer patients. Microsatellite instability phenotype is considered in this series. All patients' clinicopathological data were considered for statistical analysis and associations. Results: In this study, we verified multiple associations between oncogenic mutations and specified clinicopathological tumor features. Respectively, we identified the following significant results: 1) EGFR A13_deletions are associated with right colon carcinoma (22.2% vs. 3.3%; p<0.005), mucinous histotype (16% vs. 7.8%; p=0.042), G3 grading (19% vs. 7.3%; p=0.024) and microsatellite instability status (p<0.005); 2) PIK3CA mutations are related mucinous histotype (12% vs. 4.4%; p=0.021) 3) KRASG12 and KRASG13mutations are correlated respectively with the left (91.4% vs. 59.3%) and right (40.7% vs. 8.6%) colon cancer development (p<0.005), and finally 4) microsatellite instability is associated with right colon tumors (28.4% vs. 5.5%; p<0.005). Conclusions: Mostly, we verified a high frequency rate of the KRASG13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRASG12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right colon cancer is associated with specific molecular characteristics, in comparison to left colon tumors. These evidences, in association with specific clinicopathological data, can delineate novel approaches for the colorectal cancer classification and targeted intervention.

Effect of tumor location in metastatic colorectal cancer to response anti-EGFR and anti-VEGF treatment: One center study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15023-e15023
Author(s):  
Metin Ozkan ◽  
Ender Dogan ◽  
Mahmut Ucar ◽  
Teoman Sakalar ◽  
Ahmet Alghareeb ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Location ◽  
Left Colon ◽  
First Line ◽  
Anti Vegf ◽  
Study Population ◽  
Colorectal Cancer Patients

e15023 Background: Colorectal cancer is the one of the most common malignancy in western countries. In addition to standart treatment antiEGFR and antiVEGF agents have improved PFS and overall survival. Current studies showed that the colorectal cancers have heterogenous characteristics. The Colon is divided into two parts as a right and left colon according to embrological origin. Recent years supposed that right and left located colorectal tumors may not response samely to anti egfr and anti vegfr therapies. We performed a retrospective study in our clinic to answer this questions. Methods: Study Population and data collection: Between January 2005 and December 2016, all metastatic colorectal cancer patients (n = 285) who received anti-EGFR and anti- VEGF agent with chemotherapy on initial treatment at the Erciyes University Medical Oncology Department were retrospectively reviewed. We included patients with diagnosed metastatic colorectal cancer and who received at least 1 dose of antiEGFR-based or antiVEGFR-based triplet bio-chemotherapy as their first-line treatments. Study population was divided into two groups as right and left colon. Results: A total of 251 patients met the inclusion criteria: 55 patients classified as a right colon cancer (RCC) and 196 patients classified as a left colon cancer (LCC) . 16 patients in RCC group received anti-EGFR-based triplet and 39 patients in RCC group received antiVEGF-based triplet; 76 patients in LCC group received anti-EGFR-based triplet and 120 patients in LCC group received antiVEGF-based triplet as first-line bio-chemotherapy. There were no differences between the patients received antiEGFR and antiVEGF therapy in RCC group (PFS,antiEGFR vs anti VEGF, 7 vs 8 months,P = 0.378; OS, 21 vs 19 months, P = 0.876). There were no differences between the patients received antiEGFR and antiVEGF therapy in LCC group (PFS,antiEGFR vs anti VEGF, 10 vs 10 months,P = 0.202; OS, 27 vs 24 months, P = 0.656). Conclusions: Our study shows that there were no significiant difference between the metastatic colorectal cancer patients received antiEGFR and antiVEGF treatment in LCC and RCC.

scholarly journals Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy inKRASWild-Type Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tze-Kiong Er ◽  
Chih-Chieh Chen ◽  
Luis Bujanda ◽  
Marta Herreros-Villanueva
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Genetic Determinants ◽  
Secondary Resistance ◽  
Epidermal Growth ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Selection Of Patients ◽  
Selection Of

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit.KRASmutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction ofKRASwild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation ofBRAF,NRAS,PIK3CA, andPTENstatus could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

scholarly journals Colonoscopy Prevents Colorectal Cancer in Both the Right and Left Colon

2011 ◽  
Vol 141 (1) ◽  
pp. 393-396 ◽  
Author(s):  
Karlee J. Ausk ◽  
Jason A. Dominitz
Keyword(s):  
Colorectal Cancer ◽  
Left Colon ◽  
The Right

scholarly journals Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Takashi Kawai ◽  
Akihiro Nyuya ◽  
Yoshiko Mori ◽  
Takehiro Tanaka ◽  
Hiroaki Tanioka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylation Status ◽  
Epigenetic Alterations ◽  
Right Colon ◽  
Partial Methylation ◽  
Methylation Score ◽  
Cd8 Cell ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Clinicopathological Variables

Abstract Background Mutations in the POLE gene result in an ultra-hypermutated phenotype in colorectal cancer (CRC); however, the molecular characterisation of epigenetic alterations remains unclear. We examined the genetic and epigenetic profiles of POLE-mutant CRC to elucidate the clinicopathological features of the associated genetic and epigenetic alterations. Results Tumour tissues (1,013) obtained from a cohort of patients with CRC were analysed to determine associations between the proofreading domain mutations of POLE with various clinicopathological variables, microsatellite instability (MSI) status, BRAF and KRAS mutations, and the methylation status of key regions of MLH1, MGMT, and SFRP2 promoters by calculating the methylation scores (range 0–6). Only four cases (0.4%) exhibited pathogenic POLE hotspot mutations (two p.P286R [c.857C > G], one p.V411L [c.1231G > C], and p.S459F [c.1376C > T] each), which were mutually exclusive to BRAF and KRAS mutations and MSI. CRC patients were divided into four subgroups: patients with POLE mutations (POLE, 0.4%, n = 4), patients with both MSI and extensive methylation in MLH1 (MSI-M, 2.9%, n = 29), patients with MSI but no extensive methylation in MLH1 (MSI-U, 3.6%, n = 36), and patients without MSI (non-MSI, 93.2%, n = 944). The POLE group was younger at diagnosis (median 52 years, P < 0.0001), with frequent right-sided tumour localisation (frequency of tumours located in the right colon was 100%, 93.1%, 36.1%, and 29.9% in POLE, MSI-M, MSI-U, and non-MSI, respectively; P < 0.0001), and was diagnosed at an earlier stage (frequency of stages I–II was 100%, 72.4%, 77.8%, and 46.6% in POLE, MSI-M, MSI-U, and non-MSI, respectively, P < 0.0001). The mean methylation score in POLE was not different from that in MSI-U and non-MSI, but the methylation signature was distinct from that of the other subgroups. Additionally, although the examined number of POLE-mutant tumours was small, the number of CD8-positive cells increased in tumours with partial methylation in the MLH1 gene. Conclusions CRC patients with POLE proofreading mutations are rare. Such mutations are observed in younger individuals, and tumours are primarily located in the right colon. Diagnosis occurs at an earlier stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.

scholarly journals Post-chemotherapy bone metastasis recurrence of colorectal adenocarcinoma - case report

2018 ◽  
Vol 1 (1) ◽  
pp. 19-23
Author(s):  
Răzvan Ene ◽  
Marian Pleniceanu ◽  
Mihnea Popa ◽  
Mihai Nica ◽  
Panti Zsombor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bone Metastasis ◽  
Primary Tumor ◽  
Colorectal Adenocarcinoma ◽  
Fibular Head ◽  
Oncological Treatment ◽  
Pet Ct ◽  
Choice Of Treatment ◽  
The Right ◽  
World Ranking

AbstractOne of the most common neoplasms in the world, ranking third, is the colorectal cancer. 96% of all cases of colorectal cancer are adenocarcinoma. The prognostic of this diagnostic is a bad one, with low 5-years survival rate. Although the most common locations for the metastases are the liver and the lungs, the bones can also be targeted (5.5%).We present the case of a 65-year-old male who came to the hospital with pain and tumefaction at the right fibular head. After extensive clinical and paraclinical examinations, a biopsy was performed, at which stage the entire tumor was removed. The result was that of moderate differentiated adenocarcinoma. The patient was then further examined and a tumor was discovered at the sigmoid colon. The primary tumor was removed and the patient underwent oncological treatment. 2 years later, the patient returned with a recurrence of the bone metastasis. After a PET-CT that infirmed other metastases coupled with a satisfactory evolution of the primary tumor, the decision was made to amputate the knee above. Biopsy is an essential step that establishes the correct diagnostic and dictates the right choice of treatment solution. Counseling is also essential, so that the patient can choose and accept the best treatment option.

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